RGS-PX1, a GAP for Gα s and Sorting Nexin in Vesicular Trafficking

Author:

Zheng Bin12,Ma Yong-Chao3,Ostrom Rennolds S.4,Lavoie Christine1,Gill Gordon N.15,Insel Paul A.4,Huang Xin-Yun3,Farquhar Marilyn G.12

Affiliation:

1. Department of Cellular and Molecular Medicine,

2. Department of Pathology,

3. Department of Physiology, Weill Medical College of Cornell University, New York, NY 10021, USA.

4. Department of Pharmacology,

5. Department of Medicine, University of California San Diego, La Jolla, CA 92093–0651, USA.

Abstract

Heterotrimeric GTP–binding proteins (G proteins) control cellular functions by transducing signals from the outside to the inside of cells. Regulator of G protein signaling (RGS) proteins are key modulators of the amplitude and duration of G protein–mediated signaling through their ability to serve as guanosine triphosphatase–activating proteins (GAPs). We have identified RGS-PX1, a Gα s -specific GAP. The RGS domain of RGS-PX1 specifically interacted with Gα s , accelerated its GTP hydrolysis, and attenuated Gα s -mediated signaling. RGS-PX1 also contains a Phox (PX) domain that resembles those in sorting nexin (SNX) proteins. Expression of RGS-PX1 delayed lysosomal degradation of the EGF receptor. Because of its bifunctional role as both a GAP and a SNX, RGS-PX1 may link heterotrimeric G protein signaling and vesicular trafficking.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference28 articles.

1. G PROTEINS: TRANSDUCERS OF RECEPTOR-GENERATED SIGNALS

2. Physiological Regulation of G Protein-Linked Signaling

3. The Regulator of G Protein Signaling Family

4. Initially we identified a human cDNA clone KIAA0713 (GenBank accession number BAA34433) and several expressed sequence tags encoding an RGS protein through a BLAST search of GenBank (National Center for Biotechnology Information). A full-length cDNA (RGS-PX1 GenBank accession number ) was obtained by screening a human heart cDNA library (Stratagene) with a fragment corresponding to the putative RGS domain of KIAA0713 and subsequent 5′ rapid amplification of cDNA ends with human heart Marathon-ready cDNA (Clontech). RGS-PX1 appears to be an alternatively spliced form of KIAA0713 with a longer COOH-terminal region. The COOH-terminal region of RGS-PX1 encoding the last 362 residues is identical to a partial cDNA encoding SNX13 (GenBank accession number AAD27835). Domain analysis was done with the SMART database (5). Sequence alignment and shading were conducted with the ClustalW and MacBoxshade programs respectively. MacVector software (Oxford Molecular Madison WI) was used for transmembrane region prediction.

5. SMART: identification and annotation of domains from signalling and extracellular protein sequences

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